Field flow fractionation (FFF), pioneered by Giddings (Sep. Sci. 1966, 1, 123) is a versatile family of separation methods related to liquid chromatography. Since none of the subtechniques are utilizing a stationary phase for separation and therefore do not depend on an equilibrium process like classical chromatography, FFF is not in a strict sense a member of the family of chromatographic techniques.
FFF involves the application of an external force field to a solution, causing a migration of its constituents towards the separation channel wall. Depending on the magnitude of the force field and on chemical/physical properties, a certain solute will eventually reach a certain concentration distribution resulting in a fixed distance from the separation channel wall, this process is called relaxation. If the solution in the channel is caused to move forward in a laminar way, a parabolic flow profile will develop and the constituents will move forward with velocities equal to that axial velocity vector where most of the solute is located.
The applied field may e.g. be thermal gradients (thermal FFF), centrifugal forces (sedimentation FFF), electrical forces (electrical FFF), transverse or lateral flow (flow FFF) and transverse pressure gradients (pressure FFF). The different field types in FFF have recently been described by Janca J. (Field Flow Fractionation, Marcel Dekker: New York, 1988; Chapter 3).
The most universal FFF technique is flow FFF, which has been explored for a wide range of characterisation problems, involving virus samples (Giddings, J. C.; Yang, F. J.; Myers, M. N., J. Virol. 1977, 21, 131), proteins (Giddings, J. C.; Yang, F. J.; Myers, M. N., Anal Biochem. 1977, 81, 395), and silica sols (Giddings, J. C.; Lin, G. C.; Myers, M. N., J. Coll. Interface Sci. 1978, 65, 67) as well as synthetic polymers of both lipophilic (Brimhall, S. L.; Myers, M. N.; Caldwell, K. D.; Giddings, J. C., J. Polym. Sci. Polym. Lett. Ed. 1984, 22, 339) and hydrophilic (Giddings, J. C.; Lin, G. C.; Myers, M. N., J. Liq. Chromatogr. 1978, 1, 1) nature.
Significant technical improvements in flow FFF have been made in recent years by Wahlund and Giddings with coworkers (Wahlund, K.-G.; Winegartner, H. S.; Caldwell, K. D.; Giddings, J. C., Anal. Chem. 1986, 58, 573; Wahlund, K.-G.; Giddings, J. C., Anal. Chem. 1987, 59, 1332; and Giddings, J. C.; Xiurong, C.; Wahlund, K.-G.; Myers, M. N., Anal. Chem. 1987, 59, 1957) who obtained shorter elution times and better resolution.
Pressure FFF is a subtechnique that is closely related to flow FFF. In both flow FFF and pressure FFF a cross-flow represents the lateral field and the separation channel is almost always of the parallel plane membrane type. The principal difference between flow FFF and pressure FFF is that in flow FFF, the flow field is applied externally across the channel by a separate pump, whereas in pressure FFF the lateral flow is created by a pressure drop over the semi-permeable membrane. In 1974, Lee et al (Lee, H.-L.; Reis, J. F. G.; Dohner, J.; Lightfoot, E. N., A. I. Ch. J. 1974, 20, 776) published a paper where the first experimental work with pressure FFF in a circular channel was presented.
Doshi et al (Doshi, M. R.; Gill, W. N., Chem. Engin. Sci. 1979, 34, 725) have shown that this method in theory is expected to give better resolution than both flow FFF and pressure FFF with parallel plane membranes.